Formaldehyde → HCID 67300474, compound

HRID 1015451Notes

Reaction equation

HRID 1015451 reaction equation
Cl.[F:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([NH:19][CH:20]4[CH2:24][CH2:23][NH:22][CH2:21]4)=[O:18])=[CH:14][CH:15]=3)[C:10]([CH3:25])=[C:9]2[CH3:26])=[CH:5][CH:4]=1.C=O.[C:31](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCl.C(N(CC)CC)C>[F:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([NH:19][CH:20]4[CH2:24][CH2:23][N:22]([CH3:31])[CH2:21]4)=[O:18])=[CH:14][CH:15]=3)[C:10]([CH3:25])=[C:9]2[CH3:26])=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 67300494HCID 67300494, compound

Product 1

HCID 67300474HCID 67300474, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

A 317 mg portion of 1-(4-fluorobenzyl)-2,3-dimethyl-N-pyrrolidin-3-yl-1H-indole-5-carboxamide hydrochloride was suspended in 8 ml of dichloromethane, 0.11 ml of triethylamine and 0.13 ml of formaldehyde (a 37% aqueous solution) were added, and then 836 mg of sodium triacetoxy borohydride was added under ice-cooling, followed by stirring at room temperature for 1.5 hours. A 1 M sodium hydroxide aqueous solution was added to the reaction liquid, followed by extraction with chloroform. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After evaporation of the solvent under a reduced pressure, the residue was purified by silica gel column chromatography (chloroform:methanol:28% aqueous ammonia=100:1:0.1 to 50:1:0.1 to 30:1:0.1 to 20:1:0.1) to obtain 279 mg of 1-(4-fluorobenzyl)-2,3-dimethyl-N-(1-methylpyrrolidin-3-yl)-1H-indole-5-carboxamide as a colorless solid. This product was suspended in 2 ml of ethanol, and 0.27 ml of 4 M hydrogen chloride-ethyl acetate was added, followed by stirring at room temperature for 2 hours. After evaporation of the solvent under a reduced pressure, the residue was dissolved in 2 ml of acetone, followed by stirring at room temperature for 2 hours. The resulting solid was collected by filtration and then washed with acetone to obtain 261 mg of 1-(4-fluorobenzyl)-2,3-dimethyl-N-(1-methylpyrrolidin-3-yl)-1H-indole-5-carboxamide hydrochloride as a pale pink solid.

Workup

  1. temperaturecooling
  2. extractionfollowed by extraction with chloroform
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customAfter evaporation of the solvent under a reduced pressure
  6. customthe residue was purified by silica gel column chromatography (chloroform:methanol:28% aqueous ammonia=100:1:0.1 to 50:1:0.1 to 30:1:0.1 to 20:1:0.1)

Sources & evidence

ORD record
ord-e5d319cb7ec44acf828b29f6ba701250
Source dataset
uspto-grants-2011_07
Patent number
US07985764B2

Reaction notes

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